Development and use of an in vivo mouse model system to assess the morphological effects of exposure to endocrine disrupting compounds in uterine and mammary tissue

Endocrine disrupting compounds (EDCs) are chemicals that modify the natural actions of hormones and have the potential to impact human health. This study developed an in vivo adult mouse model system to examine the effects of controlled oral EDC administration on uterine and mammary gland morphology, and used it to determine the morphological effects of oral bisphenol A (BPA) administered alone and in combination with 17-β Estradiol (E 2 ). BPA administration at a 0.5μg to 500mg/kg/day dose range did not induce any measurable effects. However, BPA administration at a 0.5-500 mg/kg/day dose range in combination with 400μg/kg/day E 2 caused a significantly greater response at some endpoints tested compared to vehicle treated animals and animals treated with 400μg/kg/day E 2 alone in the uterus, but not the mammary gland, suggesting a selective uterine synergism. This response was not uniform across all endpoints tested and did not show evidence of a traditional dose response.